Eukaryotic protein synthesis is regulated in part by the energy state of the cell, a term denoting availability of utilizable high-energy phosphate bonds. In addition to the purine nucleotides, there is another high-energy phosphate-containing compound in muscle, creatine phosphate (CrP), which may also play a role in regulating protein synthesis. In light of the importance of maintaining normal protein balance in healthy and diseased myocardium, it is the objective of this research program to define the relation between the energy state of myocardial cells, considering CrP as well as the purine nucleotides, and the rates of synthesis of two important classes of cardiac proteins, mitochondrial and myofibrillar proteins. Large changes in energy metabolism and/or muscle protein synthesis occur during normal cardiac growth and during myocardial ischemia. Accordingly, changes in the synthesis and accumulation of myofibrillar proteins (creatine kinase isozymes and myosin), mitochondrial proteins (creatine kinase isozyme and succinate dehydrogenase) and the high-energy phosphates predominant in heart (CrP, ATP and GTP) will be measured in the developing mouse heart (fetal, neonatal and adult) and in a model of ischemia, the cultured intact beating fetal mouse heart deprived of oxygen and oxidizable substrates. Since deprivation of oxygen and oxidizable substrates simulates important characteristics of ischemia, results obtained from studying energy metabolism in deprived hearts and in hearts recovering from transient deprivation have potential application beyond the fundamental problem of how protein synthesis is regulated. These results will define factors important in regulating synthesis of the high-energy phosphate-containing compounds and hence may have application to the problem of salvaging damaged myocardial tissue following ischemic insult. As a logical extension of these in vivo and in vitro studies, experiments are proposed for later years of this research program to probe the molecular mechanisms involved in regulation of muscle protein synthesis by testing whether CrP plays a direct role in regulating initiation of contractile proteins.